We are interested in investigating a potential role for activated-complement/neutrophil interaction in pulmonary inflammation and dysfunction. In recent studies of the nature of hemodialysis neutropenia, we have demonstrated that extracorporeal complement activation (by dialysis coil cellophane) leads to increased in vitro granulocyte adhesiveness and results in pulmonary sequestration of granulocytes when the activated plasma is reinfused. The ensuing degranulation of these cells releases proteolytic lysosomal enzymes into the pulmonary microcirculation leading to endothelial damage with extravascular leak of plasma and cells. The histopathology of this pulmonary lesion is virtually identical to that of shock lung, a pulmonary dysfunction syndrome consequent to such diverse effects as shock, sepsis, and extracorporeal circulation. We believe that in this latter syndrome, complement may be activated by endotoxin in sepsis or with intestinal barrier breakdown in hemorrhagic shock, or by foreign surfaces during extracorporeal circulation. We propose to reproduce the shock lung syndrome in animals (by sepsis, hemorrhage, and extracorporeal circulation) with analysis of pulmonary function, vascular response, and granulocyte function/kinetics. Prevention of the syndrome will be attempted by depleting the animals of complement or granulocytes. If successful, an important new pathogenetic sequence of events leading to pulmonary injury will be established.